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Usage

Uses

Used in Pharmaceutical Research and Development:
4-(4-Fluorobenzoyl)piperidine is utilized as a key intermediate in the synthesis of various pharmaceutical drugs. Its unique structure allows for the creation of new compounds with potential therapeutic properties, contributing to the advancement of medicinal chemistry.
Used in Organic Synthesis:
In the field of organic synthesis, 4-(4-Fluorobenzoyl)piperidine is employed as a valuable building block for the construction of complex organic molecules. Its presence in these molecules can influence their reactivity, stability, and overall properties, making it a useful component in the synthesis of a wide range of organic compounds.
Used in Drug Design and Medicinal Chemistry:
4-(4-Fluorobenzoyl)piperidine is used as a structural element in drug design, where its incorporation into drug candidates can potentially enhance their pharmacological activity, selectivity, and efficacy. Its presence in a molecule can also contribute to improved drug delivery and bioavailability, which are critical factors in the development of effective therapeutic agents.
Used in Chemical Research:
4-(4-Fluorobenzoyl)piperidine is also used in chemical research to study the properties and reactions of compounds containing a piperidine ring and a 4-fluorobenzoyl group. This research can provide insights into the behavior of similar compounds and inform the design of new molecules with specific chemical and biological properties.

InChI:InChI=1/C12H15NO/c14-12(10-4-2-1-3-5-10)11-6-8-13-9-7-11/h1-5,11,13H,6-9H2

Upstream product

• 59084-16-1 1-acetylpiperidine-4-carbonyl chloride 
• 25519-78-2 4-(4-fluorobenzoyl)piperidine hydrochloride 
• 213886-98-7 1-acetyl-N-methoxy-N-methylpiperidine-4-carboxamide 
• 460-00-4 1-Bromo-4-fluorobenzene 
• 462-06-6 fluorobenzene 
• 498-94-2 isonipecotic acid 
• 160296-40-2 tert-butyl 1-[4-(4-fluorobenzoyl)piperidin-1-yl]carboxylate 
• 160296-41-3 4-[(4-fluorophenyl)hydroxymethyl]piperidine-1-carboxylic acid tert-butyl ester 
• 137076-22-3 tert butyl 4-formylpiperidine-1-carboxylate 
• 123855-51-6 tert-butyl 4-(hydroxymethyl)piperidin-1-carboxylate 
• 73725-76-5 4-[3-(3-chloropropoxy)-4-methoxyphenyl ]-2-pyrrolidone 
• 25503-90-6 1-acetyl-piperidine-4-carboxylic acid 
• 25519-77-1 1-(4-(4-fluorobenzoyl)piperidin-1-yl)ethanone 

Downstream Products

• 114518-17-1 (4-Fluoro-phenyl)-{1-[5-(4-fluoro-phenyl)-1H-pyrrol-2-ylmethyl]-piperidin-4-yl}-methanone 
• 144734-22-5 (4-fluorophenyl)(1-methylpiperidin-4-yl)methanone 
• 130943-94-1 (1-{3-[4-(4-Fluoro-benzoyl)-piperidin-1-yl]-propyl}-piperidin-4-yl)-(4-fluoro-phenyl)-methanone 
• 157131-42-5 2-{2-[4-(4-Fluoro-benzoyl)-piperidin-1-yl]-2-oxo-ethyl}-indan-1-one 
• 157131-44-7 N-<(1-oxo-1,2,3,4-tetrahydro-2-naphthyl)acetyl>-4-(p-fluorobenzoyl)piperidine 
• 130944-28-4 trans-1-<4-(4-fluorobenzoyl)piperidin-1-ylcarbonyl>-2-phenoxymethylcyclopropane 
• 133496-54-5 3-Benzyl-4-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-butyric acid methyl ester 
• 127625-37-0 2-<3-<4-(4-fluorobenzoyl)-1-piperidinyl>propyl>-2H-naphth<1,8-cd>isothiazole 1,1-dioxide 
• 133365-09-0 2-[3-[4-(4-fluorobenzoyl)piperidin-1-yl]propyl]-2,5,6,7,8,9-hexahydro-3H-1,2,4-triazolo[4,3-a]azepin-3-one 
• 116441-55-5 6,7-dimethoxy-3-<4-(4-fluorobenzoyl)-piperidin-1-yl>-1-methyl-4-nitroisoquinoline 
• 99228-48-5 (7R,8S)-8-{3-[4-(4-Fluoro-benzoyl)-piperidin-1-yl]-propyl}-7-hydroxy-2-methoxy-7,8-dihydro-6H-5-oxa-9-thia-benzocycloheptene-8-carboxylic acid methyl ester; hydrochloride 
• 147101-74-4 1-<2-<4-(4-fluorobenzoyl)piperidin-1-yl>ethyl>-3-(2,4-dimethoxyphenylmethyl)thieno<3,4-d>pyrimidine-2,4-dione 
• 97930-93-3 7-amino-3-(2-{4-[(4-fluorophenyl)carbonyl]piperidin-1-yl}ethyl)quinazoline-2,4(1H,3H)-dione 
• 111027-99-7 {1-[3-(4-Chloro-phenyl)-5H-benzo[b]azepin-2-yl]-piperidin-4-yl}-(4-fluoro-phenyl)-methanone 

Relevant academic research and scientific papers

Synthesis of Novel Aryloxyethylamine Derivatives and Evaluation of Their in Vitro and in Vivo Neuroprotective Activities

A series of aryloxyethylamine derivatives were designed, synthesized and evaluated for their biological activity. Their structures were confirmed by 1H-NMR, 13C-NMR, FT-IR and HR-ESI-MS. The preliminary screening of neuroprotection of compounds in vitro was detected by MTT, and the anti-ischemic activity in vivo was tested using bilateral common carotid artery occlusion in mice. Most of these compounds showed potential neuroprotective effects against the glutamate-induced cell death in differentiated rat pheochromocytoma cells (PC12 cells), especially for (4-fluorophenyl){1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}methanone, {1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}(4-methoxyphenyl)methanone, (4-bromophenyl){1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}methanone, {1-[2-(4-chlorophenoxy)ethyl]piperidin-4-yl}(4-chlorophenyl)methanone, (4-chlorophenyl)(1-{2-[(naphthalen-2-yl)oxy]ethyl}piperidin-4-yl)methanone, (4-chlorophenyl){1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}methanone and {1-[2-(4-bromophenoxy)ethyl]piperidin-4-yl}(4-chlorophenyl)methanone, which exhibited potent protection of PC12 cells at three doses (0.1, 1.0, 10 μM). Compounds (4-fluorophenyl){1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}methanone, (4-fluorophenyl){1-[2-(naphthalen-2-yloxy)ethyl]piperidin-4-yl}methanone, {1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}(4-methoxyphenyl)methanone and {1-[2-(4-chlorophenoxy)ethyl]piperidin-4-yl}(4-chlorophenyl)methanone possessed the significant prolongation of the survival time of mice subjected to acute cerebral ischemia and decreased the mortality rate at all five doses tested (200, 100, 50, 25, 12.5 mg/kg) and had significant neuroprotective activity. In addition, (4-fluorophenyl){1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}methanone, {1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}(4-methoxyphenyl)methanone and {1-[2-(4-chlorophenoxy)ethyl]piperidin-4-yl}(4-chlorophenyl)methanone possessed outstanding neuroprotection in vitro and in vivo. These compounds can be used as a promising neuroprotective agents for future development of new anti-ischemic stroke agents. Basic structure–activity relationships are also presented.

1-aryloxy ethyl piperidine-4-yl benzophenone derivative as well as preparation method and application thereof

The invention discloses a 1-aryloxy ethyl piperidine-4-yl benzophenone derivative as well as a preparation method and application thereof. The compound is a free alkali or salt with a compound of a formula (I) shown in the specification; the salt is one of hydrochloride, hydrobromide, sulfate, trifluoroacetate, tartrate, lactate or mesylate; in the formula, R1 independently represents H, halogen,alkyl, halogen-substituted alkyl, nitryl, amino, nitrile, hydroxyl, alkoxy, aryl alkoxy, heterocyclic alkoxy, aryl, substituted heterocyclic ring or substituted aryl; and R2 is independently selectedfrom H, halogen, alkyl, halogen substituted alkyl, nitryl, amino, nitrile, hydroxyl, alkoxy, aryl alkoxy, heterocyclic alkoxy, aryl, substituted heterocyclic ring or substituted aryl. The 1-aryloxy ethyl piperidine-4-yl benzophenone derivative is applied to preparation of medicines for treating cerebral arterial thrombosis.

Chemoselective generation of acyl phosphates, acylium ion equivalents, from carboxylic acids and an organophosphate ester in the presence of a Br?nsted acid

We describe the chemoselective conversion of carboxylic acids to functional aromatic ketones promoted by a tailored organophosphate ester in the presence of a Br?nsted acid. The protonated phosphate ester reacts with the carboxylic acid to form acyl phosphate, which reacts with benzenes to give aromatic ketones, probably through the acylium ion or its equivalent. The reaction time is short even at room temperature, and the reaction is compatible with various other functional groups, including amines, olefins, esters, amides and nitriles.

Discovery of 4-benzoylpiperidine and 3-(piperidin-4-yl)benzo[d]isoxazole derivatives as potential and selective GlyT1 inhibitors

Regulation of glycine transporter 1 (GlyT1) activity is a currently investigated strategy in drug discovery for schizophrenia. This study developed a series of new 4-benzoylpiperidine derivatives as GlyT1 inhibitors by bioisosteric replacement and mimicking of the pyridine ring of RG1678. Among the 4-benzoylpiperidine derivatives, 23q showed an IC50 of 30 nM. Preliminary optimization of the blood-brain barrier penetration led to the discovery of 3-(piperidin-4-yl)benzo[d]isoxazole derivatives. Both series showed good selectivity over GlyT2, D1, D2, D3, 5-HT1A and 5-HT2A receptors. Moreover, behavioral testing showed 23q (40 mg kg-1, intragastric) can inhibit the hyperlocomotion induced by acute treatment of phencyclidine, and improve the impaired negative and cognitive symptoms in chronic phencyclidine-induced C57BL/6J mice. An interesting finding showed that 3-(piperidin-4-yl)benzo[d]isoxazole was a privileged scaffold of atypical antipsychotic agents but exhibited high selectivity and potency as a GlyT1 inhibitor.

Development of Fluorine-18 Labeled Metabolically Activated Tracers for Imaging of Drug Efflux Transporters with Positron Emission Tomography

Increased activity of efflux transporters, e.g., P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), at the blood-brain barrier is a pathological hallmark of many neurological diseases, and the resulting multiple drug resistance represents a major clinical challenge. Noninvasive imaging of transporter activity can help to clarify the underlying mechanisms of drug resistance and facilitate diagnosis, patient stratification, and treatment monitoring. We have developed a metabolically activated radiotracer for functional imaging of P-gp/BCRP activity with positron emission tomography (PET). In preclinical studies, the tracer showed excellent initial brain uptake and clean conversion to the desired metabolite, although at a sluggish rate. Blocking with P-gp/BCRP modulators led to increased levels of brain radioactivity; however, dynamic PET did not show differential clearance rates between treatment and control groups. Our results provide proof-of-concept for development of prodrug tracers for imaging of P-gp/BCRP function in vivo but also highlight some challenges associated with this strategy.

Reinvestigation of the synthesis of ketanserin (5) and its hydrochloride salt (5.HCl) via 3-(2-chloroethyl)-2,4-(1H,3H)-quinazolinedione (2) or dihydro-5H-oxazole(2,3-b)quinazolin-5-one (1)

The synthesis of ketanserin (5) and its hydrochloride salt (5.HCl) using respectively equimolar amounts of 3-(2-chloroethyl)-2,4-(1H,3H)-quinazolinedione (2) with 4-(parafluorobenzoyl)piperidine (3) and dihydro-5H-oxazole(2,3-b) quinazolin-5-one (1) with hydrochloride salt of 4-(parafluorobenzoyl)piperidine (3.HCl) is reinvestigated. The one-pot reaction of ethyl-2-aminobenzoate with ethyl chloroformate and ethanol amine has afforded 3-(2-chloroethyl)-2,4-(1H,3H) -quinazolinedione (2) (86%) that was then refluxed with 4-(parafluorobenzoyl) piperidine (3) in ethyl methyl ketone in the presence of sodium carbonate to obtain free base of ketanserin (87%). In another attempt, a very pure hydrochloride salt of ketanserin (5.HCl) was synthesized using equimolar amounts of dihydro-5H-oxazole(2,3-b)quinazolin-5-one (1) and hydrochloride salt of 4-(parafluorobenzoyl)piperidine (3.HCl) by a solvent-less fusion method. Thus, under optimized conditions, 180°C and a reaction time of 30 min, the powder mixture was transformed into glassy crystals that were initially readily soluble in chloroform but were transformed afterwards over time (2 h) to white precipitates (5.HCl) suspended in chloroform with a yield of 72%.

DERIVATIVES OF TRIAZINES AND URACILS, THEIR PREPARATION AND THEIR APPLICATION IN HUMAN THERAPEUTICS

The present invention relates to derivatives of general formula I wherein : - W represents nitrogen, - R1 represents: ? a hydrogen or a linear or branched C1-C5 alkyl radical or, ? a C1-C3 alkyl radical substituted with groups such as trifluoromethyl, nitrile, hydroxy, C1-C3 alcoxy, C3-C6 alkoxyalkoxy, indolyl, thiophenyl, oxothiophenyl, C1-C3 N-alkylcarbamoyl groups or, ? a phenyl or pyridyl or naphthyl, or thiophenyl group optionally substituted with one or more groups such as halogen atoms, nitro, nitrile, trifluoromethyl, vinyl, methylsulfanyl, linear branched C1-C4 alkyl, linear or branched C1-C3 alkoxy groups, ? a C6 2-oxocycloalkyl radical - R2 represents a methyl or heptyl, - m, n are equal to 1, - V represents CH2, - X-Y represents -N- (C=O) -, -CH-O-, - Z represents a phenyl group substituted with one or more trifluoromethyl groups, halogen atoms or linear C1-C4 alkyl groups.

Syntheses and Binding Studies of New [(Aryl)(aryloxy)methyl]piperidine Derivatives and Related Compounds as Potential Antidepressant Drugs with High Affinity for Serotonin (5-HT) and Norepinephrine (NE) Transporters

In a wide search program toward new, efficient, and fast-acting antidepressant drugs, we have prepared series of new compounds having an (aryl)(aryloxy)methyl moiety linked directly or through a methylene chain to different substituted and unsubstituted cycles (isoquinoline, piperazine, piperidine, tetrahydropyran, or cyclopentane). These compounds have been evaluated for their affinities for serotonin (5-HT) transporter (SERT) and 5-HT1A and 5-HT2A receptors. Racemic mixtures of 4-[(aryl)(aryloxy)methyl]piperidine derivatives showed much higher affinity values for SERT than fluoxetine and resulted in lack of affinity for 5-HT 1A and 5-HT2A receptors. Some of these racemic mixtures were resolved to their enantiomers and tested for binding to norepinephrine (NE) transporter (NET), dopamine (DA) transporter (DAT), and α2 receptor. Several of these enantiomers [(-)-15b, (-)-15j, (-)-15t, (+)-15u] displayed a dual binding profile with affinities for SERT and NET with K i i = 1.9 and 13.5 nM, respectively), and further pharmacological characterization is in progress for its evaluation as a antidepressant.

(Aryl(alkyl)carbonyl)-heterocyclic compounds, compositions and use

The invention relates to a compound selected from those of formula (I): STR1 wherein Ar, n, B and A are as defined in the description, to their optical isomers, and to their addition salts there of with a pharmaceutically-acceptable acid or base. Medicinal product which is useful for treating pain and treating or preventing pathologies which require psychotropic agents.